Abstract 2670 Lysosome cholesterol sensing in growth regulation

Cholesterol, a key building block for cellular membranes and a precursor for steroid hormones, was recently identified as a major nutrient input that activates the master growth regulator, mammalian Target of Rapamycin Complex 1 (mTORC1) kinase. A cholesterol pool on the lysosomal limiting membrane regulates the nucleotide loading state of the heterodimeric Rag guanosine triphosphatases (GTPases). In turn, under high cholesterol the Rag GTPases promote mTORC1 recruitment to the lysosomal membrane, where mTORC1 triggers downstream programs for biomass production and suppression of catabolism.